{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,12]],"date-time":"2025-10-12T02:54:27Z","timestamp":1760237667065,"version":"build-2065373602"},"reference-count":33,"publisher":"MDPI AG","issue":"6","license":[{"start":{"date-parts":[[2020,6,5]],"date-time":"2020-06-05T00:00:00Z","timestamp":1591315200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001674","name":"Fondation Leducq","doi-asserted-by":"publisher","award":["16 CVD 05"],"award-info":[{"award-number":["16 CVD 05"]}],"id":[{"id":"10.13039\/501100001674","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100010269","name":"Wellcome Trust","doi-asserted-by":"publisher","award":["WT088134\/Z\/09\/A"],"award-info":[{"award-number":["WT088134\/Z\/09\/A"]}],"id":[{"id":"10.13039\/100010269","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100012164","name":"Mrs Gladys Row Fogo Charitable Trust","doi-asserted-by":"publisher","award":["BRO-D.FID366841"],"award-info":[{"award-number":["BRO-D.FID366841"]}],"id":[{"id":"10.13039\/100012164","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000274","name":"British Heart Foundation","doi-asserted-by":"publisher","award":["CH\/12\/4\/29762"],"award-info":[{"award-number":["CH\/12\/4\/29762"]}],"id":[{"id":"10.13039\/501100000274","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100010661","name":"Horizon 2020","doi-asserted-by":"publisher","award":["PHC-03-15, project No666881, SVDs@Target"],"award-info":[{"award-number":["PHC-03-15, project No666881, SVDs@Target"]}],"id":[{"id":"10.13039\/100010661","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["J. Imaging"],"abstract":"<jats:p>Dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) can be used to examine the distribution of an intravenous contrast agent within the brain. Computational methods have been devised to analyse the contrast uptake\/washout over time as reflections of cerebrovascular dysfunction. However, there have been few direct comparisons of their relative strengths and weaknesses. In this paper, we compare five semiquantitative methods comprising the slope and area under the enhancement-time curve, the slope and area under the concentration-time curve (    S l o p  e  C o n       and     A U  C  C o n      ), and changes in the power spectrum over time. We studied them in cerebrospinal fluid, normal tissues, stroke lesions, and white matter hyperintensities (WMH) using DCE-MRI scans from a cohort of patients with small vessel disease (SVD) who presented mild stroke. The total SVD score was associated with     A U  C  C o n       in WMH (    p &lt; 0.05    ), but not with the other four methods. In WMH, we found higher     A U  C  C o n       was associated with younger age (    p &lt; 0.001    ) and fewer WMH (    p &lt; 0.001    ), whereas     S l o p  e  C o n       increased with younger age (    p &gt; 0.05    ) and WMH burden (    p &gt; 0.05    ). Our results show the potential of different measures extracted from concentration-time curves extracted from the same DCE examination to demonstrate cerebrovascular dysfunction better than those extracted from enhancement-time curves.<\/jats:p>","DOI":"10.3390\/jimaging6060043","type":"journal-article","created":{"date-parts":[[2020,6,9]],"date-time":"2020-06-09T04:19:39Z","timestamp":1591676379000},"page":"43","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Examining the Relationship between Semiquantitative Methods Analysing Concentration-Time and Enhancement-Time Curves from Dynamic-Contrast Enhanced Magnetic Resonance Imaging and Cerebrovascular Dysfunction in Small Vessel Disease"],"prefix":"10.3390","volume":"6","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3167-5134","authenticated-orcid":false,"given":"Jose","family":"Bernal","sequence":"first","affiliation":[{"name":"Centre for Clinical Brain Sciences, University of Edinburgh, Edinburgh EH16 4SB, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2771-6546","authenticated-orcid":false,"given":"Mar\u00eda","family":"Vald\u00e9s-Hern\u00e1ndez","sequence":"additional","affiliation":[{"name":"Centre for Clinical Brain Sciences, University of Edinburgh, Edinburgh EH16 4SB, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2105-8725","authenticated-orcid":false,"given":"Javier","family":"Escudero","sequence":"additional","affiliation":[{"name":"School of Engineering, University of Edinburgh, Edinburgh EH9 3FB, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Eleni","family":"Sakka","sequence":"additional","affiliation":[{"name":"Centre for Clinical Brain Sciences, University of Edinburgh, Edinburgh EH16 4SB, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Paul A.","family":"Armitage","sequence":"additional","affiliation":[{"name":"Academic Unit of Radiology, University of Sheffield, Sheffield S10 2JF, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Stephen","family":"Makin","sequence":"additional","affiliation":[{"name":"Institute of Cardiovascular and Medical Sciences, University of Glasgow, Glasgow G12 8TA, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0670-0887","authenticated-orcid":false,"given":"Rhian M.","family":"Touyz","sequence":"additional","affiliation":[{"name":"Institute of Cardiovascular and Medical Sciences, University of Glasgow, Glasgow G12 8TA, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9812-6642","authenticated-orcid":false,"given":"Joanna M.","family":"Wardlaw","sequence":"additional","affiliation":[{"name":"Centre for Clinical Brain Sciences, University of Edinburgh, Edinburgh EH16 4SB, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2020,6,5]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"194","DOI":"10.1002\/ana.21549","article-title":"Lacunar stroke is associated with diffuse blood\u2013brain barrier dysfunction","volume":"65","author":"Wardlaw","year":"2009","journal-title":"Ann. Neurol."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"1725","DOI":"10.1212\/WNL.0b013e318236ef46","article-title":"Hyperacute injury marker (HARM) in primary hemorrhage: A distinct form of CNS barrier disruption","volume":"77","author":"Kidwell","year":"2011","journal-title":"Neurology"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"840","DOI":"10.1016\/j.jalz.2019.01.013","article-title":"Quantifying blood\u2013brain barrier leakage in small vessel disease: Review and consensus recommendations","volume":"15","author":"Thrippleton","year":"2019","journal-title":"Alzheimer\u2019s Dement."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"192","DOI":"10.1136\/jnnp.2009.172072","article-title":"Blood\u2013brain barrier permeability is increased in normal-appearing white matter in patients with lacunar stroke and leucoaraiosis","volume":"81","author":"Topakian","year":"2010","journal-title":"J. Neurol. Neurosurg. Psychiatry"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"644","DOI":"10.1177\/0271678X16635657","article-title":"Integrity of normal-appearing white matter: Influence of age, visible lesion burden and hypertension in patients with small-vessel disease","volume":"37","author":"Chappell","year":"2017","journal-title":"J. Cereb. Blood Flow Metab."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"634","DOI":"10.1016\/j.jalz.2016.09.006","article-title":"Blood-brain barrier failure as a core mechanism in cerebral small vessel disease and dementia: Evidence from a cohort study","volume":"13","author":"Wardlaw","year":"2017","journal-title":"Alzheimer\u2019s Dement."},{"key":"ref_7","doi-asserted-by":"crossref","unstructured":"Bernal, J., Vald\u00e9s-Hern\u00e1ndez, M.d.C., Escudero, J., Armitage, P.A., Makin, S., Touyz, R.M., and Wardlaw, J.M. (2019, January 24\u201326). Analysis of spatial spectral features of dynamic contrast-enhanced brain magnetic resonance images for studying small vessel disease. Proceedings of the Annual Conference on Medical Image Understanding and Analysis, Liverpool, UK.","DOI":"10.1007\/978-3-030-39343-4_24"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"240","DOI":"10.1016\/j.mri.2019.11.001","article-title":"Analysis of dynamic texture and spatial spectral descriptors of dynamic contrast-enhanced brain magnetic resonance images for studying small vessel disease","volume":"66","author":"Bernal","year":"2020","journal-title":"Magn. Reson. Imaging"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"305","DOI":"10.1016\/j.mri.2010.09.002","article-title":"Use of dynamic contrast-enhanced MRI to measure subtle blood\u2013brain barrier abnormalities","volume":"29","author":"Armitage","year":"2011","journal-title":"Magn. Reson. Imaging"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"1967","DOI":"10.1002\/mrm.25793","article-title":"Optimal acquisition and modeling parameters for accurate assessment of low Ktrans blood\u2013brain barrier permeability using dynamic contrast-enhanced MRI","volume":"75","author":"Barnes","year":"2016","journal-title":"Magn. Reson. Med."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"446","DOI":"10.1016\/j.neuroimage.2015.10.018","article-title":"Tracer kinetic modelling for DCE-MRI quantification of subtle blood\u2013brain barrier permeability","volume":"125","author":"Heye","year":"2016","journal-title":"Neuroimage"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"e00415","DOI":"10.1002\/brb3.415","article-title":"Rationale, design and methodology of the image analysis protocol for studies of patients with cerebral small vessel disease and mild stroke","volume":"5","author":"Armitage","year":"2015","journal-title":"Brain Behav."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"1003","DOI":"10.1212\/WNL.0000000000004328","article-title":"White matter hyperintensity reduction and outcomes after minor stroke","volume":"89","author":"Wardlaw","year":"2017","journal-title":"Neurology"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"1285","DOI":"10.1161\/01.STR.19.10.1285","article-title":"White matter signal abnormalities in normal individuals: Correlation with carotid ultrasonography, cerebral blood flow measurements, and cerebrovascular risk factors","volume":"19","author":"Fazekas","year":"1988","journal-title":"Stroke"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"1228","DOI":"10.1212\/WNL.0000000000000837","article-title":"Stroke subtype, vascular risk factors, and total MRI brain small-vessel disease burden","volume":"83","author":"Staals","year":"2014","journal-title":"Neurology"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"1684","DOI":"10.1007\/s00330-010-1718-6","article-title":"New multispectral MRI data fusion technique for white matter lesion segmentation: Method and comparison with thresholding in FLAIR images","volume":"20","author":"Ferguson","year":"2010","journal-title":"Eur. Radiol."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"75","DOI":"10.1016\/S0921-9366(98)80004-2","article-title":"Chapter 3 Power spectrum and its applications","volume":"Volume 5","author":"Naidu","year":"1998","journal-title":"Analysis of Geophysical Potential Fields"},{"key":"ref_18","doi-asserted-by":"crossref","unstructured":"Happ, C., and Greven, S. (2018). Multivariate functional principal component analysis for data observed on different (dimensional) domains. J. Am. Stat. Assoc., 1\u201311.","DOI":"10.1080\/01621459.2016.1273115"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"263","DOI":"10.1159\/000017248","article-title":"White matter lesions in dementia: An MRI study on blood-brain barrier dysfunction","volume":"11","author":"Bronge","year":"2000","journal-title":"Dement. Geriatr. Cogn. Disord."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1159\/000058326","article-title":"Increased blood-brain barrier permeability in white matter lesions of Binswanger\u2019s disease evaluated by contrast-enhanced MRI","volume":"14","author":"Hanyu","year":"2002","journal-title":"Dement. Geriatr. Cogn. Disord."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"1327","DOI":"10.1161\/STROKEAHA.107.500124","article-title":"Changes in background blood\u2013brain barrier integrity between lacunar and cortical ischemic stroke subtypes","volume":"39","author":"Wardlaw","year":"2008","journal-title":"Stroke"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"525","DOI":"10.1161\/STROKEAHA.112.669994","article-title":"Blood\u2013brain barrier permeability and long-term clinical and imaging outcomes in cerebral small vessel disease","volume":"44","author":"Wardlaw","year":"2013","journal-title":"Stroke"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"232","DOI":"10.1016\/j.pscychresns.2008.04.003","article-title":"Blood\u2013brain barrier permeability in Alzheimer\u2019s disease: A case\u2013control MRI study","volume":"171","author":"Starr","year":"2009","journal-title":"Psychiatry Res. Neuroimaging"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"262","DOI":"10.1016\/j.nicl.2014.09.002","article-title":"Assessment of blood\u2013brain barrier disruption using dynamic contrast-enhanced MRI. A systematic review","volume":"6","author":"Heye","year":"2014","journal-title":"NeuroImage Clin."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"56","DOI":"10.1111\/j.1365-2990.2010.01139.x","article-title":"Cerebral microvascular pathology in ageing and neurodegeneration","volume":"37","author":"Brown","year":"2011","journal-title":"Neuropathol. Appl. Neurobiol."},{"key":"ref_26","unstructured":"Heye, A.K. (2015). Measurement of Subtle Blood-Brain Barrier Disruption in Cerebral Small Vessel Disease Using Dynamic Contrast-Enhanced Magnetic Resonance Imaging. [Ph.D. Thesis, The University of Edinburgh]."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"e001140","DOI":"10.1161\/JAHA.114.001140","article-title":"What are white matter hyperintensities made of? Relevance to vascular cognitive impairment","volume":"4","author":"Wardlaw","year":"2015","journal-title":"J. Am. Heart Assoc."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"1653","DOI":"10.1177\/0271678X16662891","article-title":"Cerebral blood flow in small vessel disease: A systematic review and meta-analysis","volume":"36","author":"Shi","year":"2016","journal-title":"J. Cereb. Blood Flow Metab."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"779","DOI":"10.1016\/j.jstrokecerebrovasdis.2016.10.017","article-title":"White matter hyperintensity associations with cerebral blood flow in elderly subjects stratified by cerebrovascular risk","volume":"26","author":"Bahrani","year":"2017","journal-title":"J. Stroke Cerebrovasc. Dis."},{"key":"ref_30","doi-asserted-by":"crossref","unstructured":"Blair, G.W., Thrippleton, M.J., Shi, Y., Hamilton, I., Stringer, M., Chappell, F.M., Dickie, D.A., Andrews, P.J., Marshall, I., and Doubal, F.N. (2019). Intracranial functional haemodynamic relationships in patients with cerebral small vessel disease. bioRxiv.","DOI":"10.1101\/572818"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"35","DOI":"10.1016\/S0300-2977(98)00134-X","article-title":"Cerebral complications of diabetes: Clinical findings and pathogenetic mechanisms","volume":"54","author":"Biessels","year":"1999","journal-title":"Neth. J. Med."},{"key":"ref_32","first-page":"125","article-title":"Diabetes mellitus and blood-brain barrier dysfunction: An overview","volume":"2","author":"Prasad","year":"2014","journal-title":"J. Pharmacovigil."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"54","DOI":"10.4239\/wjd.v6.i1.54","article-title":"Pathogenesis of diabetic cerebral vascular disease complication","volume":"6","author":"Xu","year":"2015","journal-title":"World J. Diabetes"}],"container-title":["Journal of Imaging"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2313-433X\/6\/6\/43\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T09:35:53Z","timestamp":1760175353000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2313-433X\/6\/6\/43"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,6,5]]},"references-count":33,"journal-issue":{"issue":"6","published-online":{"date-parts":[[2020,6]]}},"alternative-id":["jimaging6060043"],"URL":"https:\/\/doi.org\/10.3390\/jimaging6060043","relation":{},"ISSN":["2313-433X"],"issn-type":[{"type":"electronic","value":"2313-433X"}],"subject":[],"published":{"date-parts":[[2020,6,5]]}}}